Xcelom Limited (Global)
Long-read Sequencing
Comprehensive solution for single gene disorders with complex molecular genetics
The Challenge: The Limitations of Short-Read NGS
While Next-Generation Sequencing (NGS) tools like WES and WGS are widely adopted in clinical practice, they leave a significant diagnostic gap. Current diagnostic yields remain around 30%-40%¹, partly due to the technical limitations of NGS technology, which cannot resolve the "dark regions" of the genome.
There are approximately 400 medically relevant genes that are technically challenging for NGS². Because NGS frequently misses variants in these areas, physicians often cannot identify the causative genetic factor in a single test. Consequently, they must order additional tests, making the diagnostic journey longer and more complicated for the patient.
"Dark Regions" of Short-Read NGS:
Image from Mantere T, Kersten S, Hoischen A. Long-Read Sequencing Emerging in Medical Genetics. Front Genet. 2019;10:426.
Structural Variation
Often misaligned or missed entirely
Repeat Expansion
Limited capacity to sequence the full repetitive element (e.g., VNTR)
Phasing
Cannot assign the variants to the homologous paternal or maternal chromosomes
Pseudogenes/High homology
Difficult to distinguish functional and non-functional sequence
GC-Rich Region
Amplification bias in NGS leads to poor coverage in GC-rich areas
From short-read to long-read
To bridge this gap, the community is turning to Long-Read Sequencing (LRS), also known as third-generation sequencing. Technologies like Nanopore and Single Molecule, Real-Time (SMRT) sequencing use long-reads to span the difficult regions that short-read NGS cannot map. LRS also resolves haplotype phasing, revealing hidden genomic contexts that NGS fails to access.
Among these options, SMRT technology offers a distinct advantage for clinical service laboratories. It produces high-quality data at scale, offering platform stability and the highest LRS accuracy (Quality Score >Q33) through "HiFi reads". Furthermore, SMRT is a cost-effective option for service laboratories handling high or routine sample volumes, as it is optimized as a high-throughput sequencing platform.
Global First! IVD Approval for Long-Read Sequencer
On September 29, 2025, the Sequel II CNDx system—through the long partnership of Berry Genomics and PacBio—became the world’s first LRS platform to receive IVD approval (Medical Device Registration approval from NMPA in China).
Combined with Berry Genomics' previously approved CATSA assay and software, this creates the first fully IVD-certified clinical LRS solution, setting a milestone for clinical LRS history.
Standardized LRS Solutions
Berry Genomics and Haorui Genomics offer advanced PacBio SMRT systems (Vega, Sequel II, and Revio) for whole-genome studies and target panel. Our highly experienced expert team provides complete clinical and research solutions to laboratories and clinics, such as send-out testing, custom assay development, and turnkey technology transfer packages.
Customization
Beyond the standard offerings, we can provide fully tailored LRS solutions to meet your specific project goals. Whether you require project support or wish to co-develop a custom clinical LRS panel for your laboratory, our experienced R&D team and production facilities are ready to deliver.
References:
1. Whitepaper Improving solve rates in rare disease research with HiFi long-read sequencing. PacBio Inc. Accessed June, 2025. https://precision.fda.gov/challenges/10/results
2. Wagner J, Olson ND, Harris L, et al. Curated variation benchmarks for challenging medically relevant autosomal genes. Nat Biotechnol. 2022;40(5):672-680.